Antimicrobial Peptides against Multidrug-Resistant Pseudomonas aeruginosa Biofilm from Cystic Fibrosis Patients

J Med Chem. 2022 Jul 14;65(13):9050-9062. doi: 10.1021/acs.jmedchem.2c00270. Epub 2022 Jun 27.

Abstract

Lung infection is the leading cause of morbidity and mortality in cystic fibrosis (CF) patients and is mainly dominated by Pseudomonas aeruginosa. Treatment of CF-associated lung infections is problematic because the drugs are vulnerable to multidrug-resistant pathogens, many of which are major biofilm producers like P. aeruginosa. Antimicrobial peptides (AMPs) are essential components in all life forms and exhibit antimicrobial activity. Here we investigated a series of AMPs (d,l-K6L9), each composed of six lysines and nine leucines but differing in their sequence composed of l- and d-amino acids. The d,l-K6L9 peptides showed antimicrobial and antibiofilm activities against P. aeruginosa from CF patients. Furthermore, the data revealed that the d,l-K6L9 peptides are stable and resistant to degradation by CF sputum proteases and maintain their activity in a CF sputum environment. Additionally, the d,l-K6L9 peptides do not induce bacterial resistance. Overall, these findings should assist in the future development of alternative treatments against resistant bacterial biofilms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Anti-Infective Agents* / therapeutic use
  • Antimicrobial Peptides
  • Biofilms
  • Cystic Fibrosis* / drug therapy
  • Humans
  • Microbial Sensitivity Tests
  • Pseudomonas Infections* / drug therapy
  • Pseudomonas Infections* / microbiology
  • Pseudomonas aeruginosa

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Antimicrobial Peptides